Immune-inflammatory markers of response to repetitive transcranial magnetic stimulation in depression: A scoping review.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive form of neuromodulatory therapy in patients with major depressive disorder (MDD). MDD is associated with increased peripheral and brain inflammation. The current paper aims to provide an overview of research examining the relationship between immune and inflammatory markers and response to rTMS in MDD. METHODS: A scoping review method was adopted in keeping with the PRISMA-ScR guidelines. Twelve relevant studies were retrieved from the PubMed and Scopus databases and rated for study quality using a modified version of the BIOCROSS tool. RESULTS: Response to rTMS in MDD was associated with basal and post-treatment levels of the inflammatory markers amyloid A, antithrombin III, oxidised phosphatidylcholine, and the microRNA miR-146a-5p. Inconsistent results were observed for the cytokines interleukin-1ß, interleukin-2 and tumour necrosis factor-α. Increased baseline levels of interleukin-6 and C-reactive protein were linked to a poorer response to rTMS. DISCUSSION: These results suggest that rTMS may have effects on immune-inflammatory pathways that are distinct from those of antidepressants and electroconvulsive therapy. Because of certain methodological limitations in the included studies, these results should be interpreted with caution.

Examining the Relationships between the Incidence of Infectious Diseases and Mood Disorders: An Analysis of Data from the Global Burden of Disease Studies, 1990-2019.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of 30 years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

The influence of cultural and religious factors on cross-national variations in the prevalence of chronic back and neck pain: an analysis of data from the global burden of disease 2019 study.

Introduction: Low back pain and neck pain are among the most commonly reported forms of chronic pain worldwide, and are associated with significant distress, disability and impairment in quality of life. Though these categories of pain can be analyzed and treated from a biomedical perspective, there is evidence that they are both related to psychological variables such as depression and anxiety. The experience of pain can be significantly influenced by cultural values. For example, cultural beliefs and attitudes can influence the meaning attached to the experience of pain, the responses of others to a sufferer's pain, and the likelihood of seeking medical care for particular symptoms. Likewise, religious beliefs and practices can influence the both experience of pain and the responses to it. These factors have also been associated with variations in the severity of depression and anxiety. Methods: In the current study, data on the estimated national prevalence of both low back pain and neck pain, obtained from the 2019 Global Burden of Disease Study (GBD 2019), is analyzed in relation to cross-national variations in cultural values, as measured using Hofstede's model (n =115 countries) and in religious belief and practice, based on the most recent Pew Research Center survey (n = 105 countries). To address possible confounding factors, these analyses were adjusted for variables known to be associated with chronic low back or neck pain, namely smoking, alcohol use, obesity, anxiety, depression and insufficient physical activity. Results: It was found that the cultural dimensions of Power Distance and Collectivism were inversely correlated with the prevalence of chronic low back pain, and Uncertainty Avoidance was inversely correlated with the prevalence of chronic neck pain, even after adjustment for potential confounders. Measures of religious affiliation and practice were negatively correlated with the prevalence of both conditions, but these associations were not significant after adjusting for cultural values and confounders. Discussion: These results highlight the existence of meaningful cross-cultural variations in the occurrence of common forms of chronic musculoskeletal pain. Psychological and social factors that could account for these variations are reviewed, along with their implications for the holistic management of patients with these disorders.

Biomarkers of Neurodegeneration in Post-Traumatic Stress Disorder: An Integrative Review.

Post-Traumatic Stress Disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer's dementia and Parkinson's disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders and would also help in the development of preventive strategies for neurodegenerative disorders in PTSD. With this background, the PubMed and Scopus databases were searched for studies designed to identify biomarkers that could be associated with an increased risk of neurodegenerative disorders in patients with PTSD. Out of a total of 342 citations retrieved, 29 studies were identified for inclusion in the review. The results of these studies suggest that biomarkers such as cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome, and objectively documented parasomnias are significantly associated with PTSD and may predict an increased risk of subsequent neurodegenerative disorders. The biological mechanisms underlying these changes, and the interactions between them, are also explored. Though requiring replication, these findings highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders and suggest potentially valuable avenues for prevention and early intervention.

Cultural collectivism, intimate partner violence, and women's mental health: An analysis of data from 151 countries.

Culture, defined as the distinctive, learned beliefs and patterns of behavior that are particular to a given group or community, is a key determinant of mental health. The cultural dimension of individualism-collectivism, which measures the extent to which a given society accords importance to individuals as opposed to larger groups, has been associated with cross-national variations in mental health outcomes such as depression and suicide. However, this cultural dimension is also associated with variations in the frequency of intimate partner violence (IPV), which has a significant and sustained adverse impact on women's mental health. This study examines the relationships between individualism-collectivism, the frequency of IPV, and rates of depression and suicide in women, based on data from 151 countries. In this data set, IPV was significantly associated with age-standardized rates of depression and suicide in women, even after adjusting for demographic variables. Cultural collectivism was positively correlated with IPV, but this relationship was significantly influenced by national income and women's educational attainment. In multivariate analyses, IPV, but not cultural collectivism, remained significantly associated with depression in women. These results highlight the importance of screening for and addressing IPV in women seeking mental health care, particularly in low- and middle-income countries where cultural and economic factors may both increase the risk of IPV and delay or impede its reporting.

The association between nation-level social and economic indices and suicide rates: A pilot study.

Ever since the pioneering work of Emile Durkheim, it has been known that regional or national suicide rates can be influenced by a variety of social and economic factors. Recent research has found a robust association between two country-level economic indices-gross national product and unemployment rate-and suicide rates, particularly in men. However, the association between other country-level social indices-such as measures of social integration, inequality, environmental preservation and political freedom-and suicide rates has not been studied at the cross-national level. In the current study, national suicide rates for men and women were examined in relation to seven indices measuring subjective wellbeing, sustainable development, type of political regime, economic and gender inequality, and social capital. It was found that the Happy Planet Index, a composite measure of subjective wellbeing and sustainable development, was negatively associated with suicide rates independent of gender, and even after adjusting for possible confounding factors. Economic inequality was associated with suicide in men, and social capital was associated with suicide in women. Moreover, the strength and direction of the associations observed between socioeconomic indices and suicide varied across income groups. These results highlight the need for a closer evaluation of the link between large-scale ("macro") social factors and individual ("micro") psychological factors, as well as the importance of integrating these factors into suicide prevention programmes at the national level.

Risperidone response in patients with schizophrenia drives DNA methylation changes in immune and neuronal systems.

Background: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material & methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences.

The most common way to treat schizophrenia is antipsychotic medication. However, not all antipsychotics work for all patients. The only way to find a suitable antipsychotic is to prescribe one and wait, sometimes for months, to see if it works. Finding an alternative to this trial-and-error method would help reduce patient suffering and costs for healthcare systems. The idea is to look in the DNA of our blood cells for specific marks that can change in response to our lifestyle or health condition. These marks could help us predict how patients will react to the drug. In other words, they can serve as biomarkers of antipsychotic response. The current work examined the blood of schizophrenia patients before and 4 weeks after starting medication. The patients who did not respond well to the drug had different marks on the genes involved in immune defense and nervous system functioning. Some of these genes also play roles in the development of schizophrenia, whereas others can directly affect what happens to the drug in the patient's body. Although marks that predict how patients will react were not identified with certainty, valuable targets for future research were identified.

Cultural values and changes in happiness in 78 countries during the COVID-19 pandemic: An analysis of data from the World Happiness Reports.

The concept of happiness is consistent across cultures to a significant extent, and encompasses both internal (subjective) and external (situational) aspects. Cultural values and norms shape emotions and behavior from an early age, and hence play a key role in influencing cross-national variations in happiness. Cross-national variations in culture can thus play a key role in influencing the relationship between adverse circumstances, such as the COVID-19 pandemic, and happiness. The current study examines the relationship between the six dimensions of culture, defined by Hofstede and his colleagues, and subjective ratings of happiness in 78 countries, obtained before (2017-19) and during (2020-21) the COVID-19 pandemic, based on data from the most recent World Happiness reports. The key results were: (a) countries were as likely to experience an increase as a decrease in self-reported happiness during this period; (b) distinct domains of culture were significantly correlated with happiness at each time point, though there was a certain degree of overlap; (c) pre-pandemic levels of happiness were negatively associated with changes in happiness during the pandemic; and (d) among cultural dimensions, long-term orientation was positively associated with changes in subjective happiness, while indulgence was negatively associated with this variable. Certain cultural values may play an important part in fostering a path to well-being in the face of stressful or traumatic circumstances. This path may be similar to the concept of mature happiness, derived from existential philosophy, which is characterized by achieving a balance between the positive and negative aspects of one's life.

The pattern of inpatient psychiatry admissions at a general hospital psychiatry unit in South India: A retrospective study.

Background: Mental illnesses are becoming a major health issue across the world. The availability of inpatient facilities for mentally ill patients is very much limited in developing countries such as India. Aim: This study was aimed to explore the pattern of psychiatric admissions at a general hospital psychiatry unit (GHPU) in South India. Methodology: The study was conducted at a multispecialty tertiary care hospital in South India. A retrospective, chart-based study design was adopted to achieve the objectives. All inpatient case records available from the department of psychiatry, the medical records department, and the electronic hospital information system of the institute were reviewed between April 2006 and March 2016. Results: A total of 3082 patients were admitted as psychiatry inpatients during the 10-year study period, representing an average of 308.2 admissions per calendar year. The majority of inpatients were male (n = 1824; 59.2%). Concerning diagnostic categories, mood disorders were accounted for 33.6% of admissions, followed by psychotic disorders (26.4%) and substance use disorders (19.3%), respectively. The median length of hospital stay was 14 days (range 0-163 days). A statistically significant seasonality pattern was noticed for mood disorders (December to February) and anxiety and neurotic disorders (August to October). Conclusion: It is obvious that treatment-seeking attitude among individuals with mental illnesses is increasing and the awareness regarding treatment aspects is also increasing among the general public. Hence, there is a need to improve the existing resources to facilitate intensive management for better treatment outcomes and this, in turn, will enhance the quality of life of mentally ill individuals.

Antipsychotics in the Management of Disruptive Behavior Disorders in Children and Adolescents: An Update and Critical Review.

Disruptive behaviour disorders (DBDs) in childhood include conduct disorder (CD) and oppositional defiant disorder (ODD). Though psychological therapies are considered to be the first-line treatment for DBDs, many patients require adjunctive pharmacotherapy for the control of specific symptoms, such as aggression. Three prior systematic reviews have examined the evidence for the use of antipsychotics in DBDs and have concluded that their efficacy is marginal and limited by adverse effects. This paper has two objectives: (i) to summarize the findings of existing systematic reviews of antipsychotics for the management of DBDs in children and adolescents (2012-2017), and (ii) to provide an update to these reviews by examining recent clinical trials of antipsychotics in this population, published in the period from 2 January 2017 to 10 October 2022. The PubMed, Scopus and ScienceDirect databases were searched for relevant citations using the search terms "disruptive behaviour disorder", "oppositional defiant disorder", "conduct disorder" and their variants, along with "antipsychotic", "atypical antipsychotic" and the generic names of all currently approved atypical antipsychotics. Six relevant trials were identified during this period, including five randomized controlled trials and one naturalistic open-label trial. These trials were critically evaluated in terms of outcome measures, efficacy and safety. Overall, the data from these trials suggests that of all available antipsychotics, risperidone appears to be effective in the short-term management of DBDs. All available antipsychotics are associated with significant metabolic adverse effects in this population. These results are discussed in the light of global trends towards increasing off-label prescription of antipsychotic medication in children and adolescents and of recent literature on the neuropharmacology of aggression in this patient population. The need for rational, short-term use of these drugs is highlighted, as well as the importance of post-marketing surveillance for long-term or severe adverse events.

Dissociative Symptoms and Disorders in Patients With Bipolar Disorders: A Scoping Review.

Dissociative disorders are an important group of trauma-related disorders associated with significant disability. The co-occurrence of dissociative disorders (DD) and symptoms (DS) in bipolar disorder has been relatively understudied, but there is some evidence that this comorbidity may have significant mechanistic and clinical implications. This paper presents the results of a scoping review of the frequency and correlates of DS and DD in bipolar disorder. Based on the available evidence, DS/DD are more common in bipolar disorder than in healthy controls or in unipolar depression, are related to childhood trauma, and are associated with psychotic symptoms, suicide attempts, and a poorer response to treatment in patients with bipolar disorder. The implications of these findings, and possible mechanistic pathways underlying them, are discussed based on the current literature. Clinicians should be aware of the frequent occurrence of significant DS or DD when treating patients with bipolar disorder. A tentative future research agenda for this field, based on clinical, risk factor-related and neurobiological considerations, is outlined.

Effectiveness of Family-Focused Nurse-led Intervention on Functional Improvement of Patients with Bipolar Disorder at a Tertiary Hospital in South India: A Randomized Controlled Trial.

Background: Bipolar affective disorder (BPAD) is a chronic, episodic illness that can create problems and disruptions in the social, occupational, and family functioning of a client. Families are frequently most affected by their bipolar member and have a sense of helplessness to fix bipolar symptoms. The current study aimed to assess the effectiveness of Family-focused Nursing Interventions (FFNI) on functional improvement in the sample of symptomatic bipolar affective disorder clients. Method: In this experimental study, 149 patients with BPAD were interviewed along with family members through the consecutive sampling technique from the inpatient ward. Varying block randomization was used to allocate the patients to the control and experimental groups. After obtaining ethical clearance, the study was registered under the Clinical trail registry India (CTRI). Baseline sociodemographic and clinical variables, and the functional levels, were assessed using Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool and Functional Assessment Short Test. The control group (74) received routine treatment; the experimental group (75) received routine treatment along with FFNI in seven sessions, and posttest was conducted at discharge, one-month, and at two-month follow-up at OPD. The collected data were analyzed using SPSS 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows Version 20.0, Armonk, NY: IBM Corp.), independent sample t-test, analysis of variance, and Pearson correlation used. A P-value of less than 0.05 was considered as a statistically significant result. Results: At the end of the study, 149 clients completed the treatment and follow-up. Both the groups were comparable at baseline in demography as well as clinical variables. There was significant improvement in the functional level after FFNI. The total score of LIFE-RIFT and the Functional Assessment Short Test score were significantly lower in the experimental group than the control group with P = 0.001. Conclusion: The current study concluded that adjuvant to routine treatment FFNI will improve the functional ability of the client along with routine psychiatric treatment for BPAD.

The Contributions of Pandemic Severity, Government Stringency, Cultural Values and Internet Usage to Post-traumatic Stress Disorder During the COVID-19 Pandemic: An Analysis of Data From 35 Countries.

Emergent symptoms of post-traumatic stress disorder (PTSD) have been frequently reported in the context of the COVID-19 pandemic, and may affect up to 17-18% of individuals. There is preliminary evidence that pandemic severity, cultural values, restrictions imposed by governments, and Internet usage may all influence the emergence of PTSD symptomatology. In this study, possible linear- and non-linear associations between these factors and the prevalence of PTSD symptoms across 35 countries were examined based on data from existing research. Evidence was found for a positive logarithmic relationship between the COVID-19 case-fatality ratio and PTSD (p = 0.046), a positive logarithmic relationship between power distance and PTSD (p = 0.047), and a trend toward a negative quadratic association with Internet usage (p = 0.051). No significant cross-national effect was observed for government restrictiveness. These findings suggest that strategies aimed at minimizing COVID-19 deaths, and at ensuring equitable access to essential resources, may be of use in reducing the emergence of PTSD symptoms at a population level during this pandemic.

The Molecular Genetics of Dissociative Symptomatology: A Transdiagnostic Literature Review.

Dissociative disorders are a common and frequently undiagnosed group of psychiatric disorders, characterized by disruptions in the normal integration of awareness, personality, emotion and behavior. The available evidence suggests that these disorders arise from an interaction between genetic vulnerability and stress, particularly traumatic stress, but the attention paid to the underlying genetic diatheses has been sparse. In this paper, the existing literature on the molecular genetics of dissociative disorders, as well as of clinically significant dissociative symptoms not reaching the threshold of a disorder, is reviewed comprehensively across clinical and non-clinical samples. Association studies suggest a link between dissociative symptoms and genes related to serotonergic, dopaminergic and peptidergic transmission, neural plasticity and cortisol receptor sensitivity, particularly following exposure to childhood trauma. Genome-wide association studies have identified loci of interest related to second messenger signaling and synaptic integration. Though these findings are inconsistent, they suggest biologically plausible mechanisms through which traumatic stress can lead to pathological dissociation. However, methodological concerns related to phenotype definition, study power, and correction for the confounding factors limit the value of these findings, and they require replication and extension in studies with better design.

Is There a Relationship Between ADHD and COVID-19 Prevalence and Mortality Indices? An Analysis of Data From 156 Countries.

OBJECTIVE: To examine the relationship between nation-level prevalence of ADHD and COVID-19 prevalence and mortality indices. METHOD: Associations between nation-wise estimated prevalence, crude mortality rates and case-fatality ratios for COVID-19 and estimated prevalence rates for ADHD were examined, controlling for medical conditions known to be associated with COVID-19 outcome, as well as demographic, climate-related, and economic variables. RESULTS: Prevalence of ADHD was positively correlated with COVID-19 prevalence and crude mortality rates on bivariate analyses, though the strength of this association was low. On multivariate regression, prevalence of ADHD was negatively associated with COVID-19 prevalence and crude mortality rates, though only the former finding was statistically significant. CONCLUSION: The association between ADHD and COVID-19 prevalence and mortality at a national level is inconsistent, modest, and may be largely due to confounding factors such as age, lifestyle factors, and medical comorbidities.

Diagnosis, prognosis, and treatment of brief psychotic episodes: a review and research agenda.

Brief psychotic episodes represent an intriguing paradox in clinical psychiatry because they elude the standard knowledge that applies to the persisting psychotic disorders such as schizophrenia. This Review describes key diagnostic considerations such as conceptual foundations, current psychiatric classification versus research-based operationalisations, epidemiology, and sociocultural variations; prognostic aspects including the risk of psychosis recurrence, types of psychotic recurrences, other clinical outcomes, prognostic factors; and therapeutic issues such as treatment guidelines and unmet need of care. The advances and challenges associated with the scientific evidence are used to set a research agenda in this area. We conclude that brief psychotic episodes can be reconceptualised within a clinical staging model to promote innovative translational research and improve our understanding and treatment of psychotic disorders.

Particulate Air Pollution and Risk of Neuropsychiatric Outcomes. What We Breathe, Swallow, and Put on Our Skin Matters.

We appraise newly accumulated evidence of the impact of particle pollution on the brain, the portals of entry, the neural damage mechanisms, and ultimately the neurological and psychiatric outcomes statistically associated with exposures. PM pollution comes from natural and anthropogenic sources such as fossil fuel combustion, engineered nanoparticles (NP ≤ 100 nm), wildfires, and wood burning. We are all constantly exposed during normal daily activities to some level of particle pollution of various sizes-PM2.5 (≤2.5 µm), ultrafine PM (UFP ≤ 100 nm), or NPs. Inhalation, ingestion, and dermal absorption are key portals of entry. Selected literature provides context for the US Environmental Protection Agency (US EPA) ambient air quality standards, the conclusions of an Independent Particulate Matter Review Panel, the importance of internal combustion emissions, and evidence suggesting UFPs/NPs cross biological barriers and reach the brain. NPs produce oxidative stress and neuroinflammation, neurovascular unit, mitochondrial, endoplasmic reticulum and DNA damage, protein aggregation and misfolding, and other effects. Exposure to ambient PM2.5 concentrations at or below current US standards can increase the risk for TIAs, ischemic and hemorrhagic stroke, cognitive deficits, dementia, and Alzheimer's and Parkinson's diseases. Residing in a highly polluted megacity is associated with Alzheimer neuropathology hallmarks in 99.5% of residents between 11 months and ≤40 y. PD risk and aggravation are linked to air pollution and exposure to diesel exhaust increases ALS risk. Overall, the literature supports that particle pollution contributes to targeted neurological and psychiatric outcomes and highlights the complexity of the pathophysiologic mechanisms and the marked differences in pollution profiles inducing neural damage. Factors such as emission source intensity, genetics, nutrition, comorbidities, and others also play a role. PM2.5 is a threat for neurological and psychiatric diseases. Thus, future research should address specifically the potential role of UFPs/NPs in inducing neural damage.